Defining and targeting wild-type BRCA high-grade serous ovarian cancer : DNA repair and cell cycle checkpoints

Introduction: Molecular analyzes including molecular descriptor/phenotype interactions have led to better characterization of epithelial ovarian cancer patients, including a definition of a BRCA wild-type (BRCAwt) phenotype. Understanding how and when to use agents targeted against dependent BRCAwt pathways or other molecular events at disease progression is an important translational and therapeutic direction in ovarian cancer research. Areas covered: In this overview, we provide definitions and descriptions of a BRCAwt genotype and phenotype. We discuss novel investigational drugs that hold promise for the treatment of BRCAwt ovarian cancer, including inhibitors of poly(ADP-ribose) polymerase, ribonucleotide reductase, DNA protein kinase-catalytic subunit, ataxia-telangiectasia-mutated kinase (ATM), ataxia-telangiectasia mutated and Rad3-related kinase (ATR), CHK 1/2, cyclin kinases, glutaminase-1, WEE1 kinase, as well as tumor microenvironment and angiogenesis inhibitors. This article explores the known and the emerging areas of clinical research on patients with BRCAwt ovarian cancer. Expert opinion: Discovery of molecular changes tied to annotated disease information, along with an expanding array of pathway targets and targeted therapeutic agents, creates optimism and opportunity for women with ovarian cancer. Using precision oncology approaches, clinical researchers are, and will be, poised to select more effective treatments for ovarian cancer patients.

Medienart:

E-Artikel

Erscheinungsjahr:

2019

Erschienen:

2019

Enthalten in:

Zur Gesamtaufnahme - volume:28

Enthalten in:

Expert opinion on investigational drugs - 28(2019), 9 vom: 11. Sept., Seite 771-785

Sprache:

Englisch

Beteiligte Personen:

Ivy, S Percy [VerfasserIn]
Kunos, Charles A [VerfasserIn]
Arnaldez, Fernanda I [VerfasserIn]
Kohn, Elise C [VerfasserIn]

Links:

Volltext

Themen:

ATM
ATR
Antineoplastic Agents
BRCA wild type
BRCA1 Protein
BRCA1 protein, human
BRCA2 Protein
BRCA2 protein, human
BRCAwt
Biomarkers
CHK1
CHK2
Cell cycle
DNA damage repair
DNA repair deficiencies
DNA-PKcs
Drugs, Investigational
High grade serous ovarian cancer
Homologous recombination
Immune checkpoint inhibitors
Journal Article
PARP
Review

Anmerkungen:

Date Completed 24.10.2019

Date Revised 24.10.2019

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1080/13543784.2019.1657403

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM300593945